In DRG11 knock-out mice, trigeminal cell death is extensive and does not account for failed brainstem patterning

Abstract

A previous study (Ding et al., 2003) showed that the homeodomain transcription factor DRG11 is necessary for pattern formation in the trigeminal nucleus principalis (PrV), the requisite brainstem nucleus for development of the whisker-to-barrel cortex pathway. However, it is not known how DRG11 contributes to pattern formation. Anatomical studies were performed in DRG11 knock-out (-/-) and DRG11/Bax double -/- mice to test the hypotheses that DRG11 is required for neuronal survival in the V pathway and that PrV cell death is sufficient to explain pattern alterations. At birth, DRG11(-/-) mice had equivalent cell loss in the V ganglion, PrV, and spinal V subnucleus interpolaris (SpVi). Because whisker-related patterns were normal in the SpVi, cell death would not appear to explain failed pattern formation in the mutant PrV. Electron microscopy revealed exuberant apoptosis and necrosis as the mechanisms of PrV cell death occurring in the late prenatal and newborn DRG11(-/-), when such cell death was up to six times more prevalent than normal. DRG11 heterozygote and Bax(-/-) mice were crossed in an attempt to dissociate PrV patterning anomalies from exuberant apoptosis in DRG11(-/-) mice. Both DRG11(-/-) and DRG11/Bax double -/- mutants lacked whisker-related patterning in their PrV, despite Bax(-/-)-induced rescue of V ganglion and PrV cells. Thus, apoptotic cell death is not a sufficient cause of failed pattern formation in the PrV of the DRG11(-/-). A signaling pathway involving DRG11 may, therefore, be the elusive PrV pattern maker.

HPAN: A BioMed 21 IRC

The Hope Center Program on Protein Aggregation and Neurodegeneration (HPAN) is the most formalized of the Hope Center Research Groups. HPAN, led by Co-Directors Alison Goate and David Holtzman, is one of five Interdisciplinary Research Centers (IRCs) based in the new BJC Institute of Health. This group focuses on the shared mechanism of protein aggregation that underlies numerous neurological disorders. Read more about HPAN....